Risk of Hypersensitivity Reactions to Iopromide After Intra-Arterial Versus Intravenous Administration: A Nested Case-Control Analysis of 133,331 Patients

OBJECTIVE: The aim of this study was to compare the risk of hypersensitivity reactions to iopromide after intra-arterial (IA) administration and intravenous (IV) administration. MATERIALS AND METHODS: Four observational studies were pooled. Almost half of the study population (48.1%) was from Europe, and one quarter each from China (27.6%) and other Asia countries (24.1%). All patients received iopromide either intra-arterially or intravenously for angiographic procedures (mostly cardio-angiography) or contrast-enhanced computed tomography. A nested case-control analysis, including a multivariable logistic regression model, was performed. Cases were defined by patients with a typical and unequivocal hypersensitivity (assumed non–IgE-mediated) reaction; controls were patients without any recorded reaction. The primary target variable is the odds ratio of having a hypersensitivity reaction after IA versus IV administration. RESULTS: A total of 133,331 patients met the inclusion criteria, 105,460 and 27,871 patients received iopromide IV or IA, respectively. Hypersensitivity reactions were recorded for 822 patients, and 132,509 patients served as controls. Major risk factors for hypersensitivity reactions were method of injection (IV vs IA), age (18 to <50 years vs ≥65 years), history of allergy or previous contrast media reaction (all P < 0.001), and asthma (P = 0.005). A total of 766 patients (0.7%) and 56 patients (0.2%) were recorded with hypersensitivity reactions after IV or IA administration, respectively (P < 0.0001). Adjusted odds ratio (IA vs IV) was 0.23 (95% confidence interval, 0.16–0.32) for all countries together: for China only, 0.22 (0.11–0.44); for all countries without China, 0.36 (0.25–0.53). Most frequent reactions were erythema/urticaria/rash, pruritus, and cough/sneezing. CONCLUSIONS: Hypersensitivity reactions to iopromide were significantly less frequently recorded after IA administrations. This could be related to the delayed and diluted arrival of iopromide to the lungs.